A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma

Completed · Phase 1/Phase 2

Conditions studied: Malignant Melanoma

In brief

This study aims to evaluate safety and effect of combining an oncolytic adenovirus (delolimogene mupadenorepvec; LOAd703) with atezolizumab in patients with melanoma. LOAd703 will be administered intratumorally for up to 12 injections while atezolizumab will be administered intravenously for the duration of the active study visits (up to 57 weeks). The patients are then monitored for survival for maximum study participation of 48 months. The treatments will be given every 3 weeks. The patients will then be monitored for toxicity, PK, ADA, immune responses, virus shedding, tumor response by RECIST 1.1 and survival.

Key facts

Study ID

NCT04123470

Run by

Lokon Pharma AB

People needed

24

Starts

2020-01-28

Expected to finish

2023-07-30

Last updated by the study team

2024-09-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Pathological confirmation of melanoma.
• A life expectancy of at least 3 months as per the investigator
• Valid for Swedish patients: Patients has locally advanced melanoma or metastatic melanoma, but not eligible for complete resection of melanoma Valid for US patients: Patients has locally advanced melanoma or metastatic melanoma.
• The patient has measurable disease (e.g., measurable tumor lesions must be present that can accurately be measured in at least one dimension with a minimum size of 10 mm by CT scan and MRI, 10 mm caliper measurement by clinical exam (when superficial), and/or 20 mm by chest X-ray).
• Patient has at least one injectable tumor lesion that has not been irradiated or has been irradiated but disease progression documented at the site subsequent to radiation therapy.
• The patient has received appropriate treatment with an anti-PD-1 or anti-PD-L1 antibody with or without an anti-CTLA4.
• Valid for Swedish patients: Patients whose advanced melanoma has a B-Raf mutation must have received appropriate therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor Valid for US patients: Patients whose advanced melanoma has a B-Raf mutation may have received appropriate therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor as assessed by the investigator.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Serum albumin ≥ 2.5 mg/dL.
• Absolute neutrophil count (ANC) ≥1.0 x 10e9/L.
• Platelet count ≥ 100 x 10e9/L.
• Prothrombin (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 times ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤ 1.5 times the ULN.
• Bilirubin < 1.5 times the institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 (≤ 5 if liver metastases are present) times the institutional ULN.
• The patient must have signed informed consent.

You may not qualify if…

• Malignant melanoma that is uveal.
• Subjects considered by the investigator to have rapid clinical progression due to melanoma
• Subjects must not have greater than 3 cerebral melanoma metastases, and/or clinically active cerebral melanoma metastases, and/or a requirement for corticosteroid therapy, and/or carcinomatous meningitis regardless of clinical stability.
• Any concurrent treatment that would interfere with the effect mechanisms of atezolizumab and LOAd703, including, but not limited to, continuous high-dose corticosteroids (>10 mg per day), lymphodepleting antibodies, or cytotoxic agents.
• Treatment with inhibitors of immune function, such as lymphotoxic monoclonal antibodies (e.g., alemtuzumab), or rapamycin/rapamycin analogs, or cytotoxic agents within 21 days of the first dose of LOAd703/atezolizumab.
• Therapeutic treatment with systemic antibiotics within 14 days of the first dose of LOAd703/atezolizumab.
• Treatment with biologic therapy within 21 days of the first dose of LOAd703/atezolizumab.
• Treatment with cytotoxic anticancer therapy within 14 days of the first dose of LOAd703/atezolizumab.
• Treatment with wide-field radiation within 14 days of the first dose of LOAd703/atezolizumab.
• Prior treatment with an adenovirus-based gene therapy.
• Use of any investigational agents within 21 days of the first dose of LOAd703/atezolizumab.
• The use of systemic immunostimulatory agents (including, but not limited to, interferons and IL2) are prohibited within 21 days or 5 half-lives (whichever is longer) of the first dose of LOAd703/atezolizumab.
• Failed resolution/improvement of AEs including those related to anti-PD-1/anti-PD-L1 to grade 0-1 and requirement for treatment with >10 mg/day prednisone (or equivalent) for at least two weeks prior to registration.
• History of CTCAE grade 4 immune-related AEs from monotherapy using an anti-PD-1/anti-PD-L1 antibody.
• History of CTCAE grade 4 AE that require steroid treatment (>10 mg/day prednisone or equivalent) for >12 weeks.
• Patients requiring warfarin are not eligible (low molecular weight heparin is permitted).
• Women who are pregnant (as confirmed by pregnancy test during screening in applicable patients), breastfeeding, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable highly effective contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since her last menstrual period. The following are acceptable as highly effective contraceptive methods: combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized partner or abstinence of heterosexual intercourse during the entire study period (depending on the preferred and usual life style of the subject).
• Men who do not consent to the use of condoms during intercourse during study participation or has a partner of childbearing potential, who will not use any of the highly effective contraceptive methods exemplified in exclusion criteria no 18.
• Known active hepatitis B or C infection, or HIV infection.
• Patients with active, severe autoimmune disease or immune deficiency or previous Guillain-Barré syndrome. Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover <10% of body surface area.
• Disease is well-controlled at baseline and requires only low-potency topical corticosteroids.
• Occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of leptomeningeal disease.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).

Where it is running

• Cedars-Sinai Medical Center, The Angeles Clinic and Research Institute — Los Angeles, California, United States
• Baylor St Luke's Medical Center — Houston, Texas, United States
• Uppsala University Hospital — Uppsala, Sweden

Full record on ClinicalTrials.gov

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